The FDA has issued a letter to healthcare providers that they should monitor patients with a type of peripheral arterial disease (PAD) who have been treated with vascular balloons that were coated with paclitaxel or stents that release paclitaxel in the femoropopliteal artery in the leg.1

The letter follows a meta-analysis that was recently published in the Journal of the American Heart Association (JAHA; CRD42018099447), which suggested that there is a possible increased risk of death ≥2 years in patients with PAD treated with these devices compared with control devices, which consist of noncoated balloons or bare metal stents. The specific cause of this mortality observation has not yet been determined, the agency stated.

In the letter, the agency recommended physicians monitor patients who have been treated with the coated balloons and eluting stents, and discuss the benefits and risks of all available therapies for patients with PAD. The FDA also said that, currently, the benefits continue to outweigh the risks when the devices are used as indicated. Additionally, all observed or suspected adverse events associated with these devices should be reported.

The paclitaxel-coated balloons and paclitaxel-eluting stents are approved by the FDA to treat obstructed lesions in arteries of the legs. Mechanistically, the balloon and stent operate to open the obstructed vessel, and paclitaxel is released from the balloon or stent to prevent scar tissue formation in the blood vessel that can re-obstruct the artery.

The FDA also noted in a press release that it is currently evaluating the available long-term follow-up data to determine whether there are any associated long-term risks with paclitaxel-coated products. Additional statistical analyses are also being conducted to identify the magnitude and presence of any long-term risks.

In the JAHA study, investigators conducted a systemic review and meta-analysis of 28 randomized controlled trials of paclitaxel-coated devices in the femoral and/or popliteal arteries with a primary endpoint of all-cause patient death. Risk ratios and risk differences were pooled with a random effects model, and 4663 patients (89% intermittent claudication) were analyzed.

Of 28 trials with 4432 cases, the all-cause patient death at 1 year was similar between paclitaxel-coated devices and the control arm at 2.3% versus 2.3% (Risk ratio, 1.08; 95% CI, 0.72-1.61). At 2 years, the all-cause death at 2 years—which was 12 trials and 2316 cases—was significantly higher in the paclitaxel arm (7.2%) than in the control arm (3.8%; risk ratio, 1.68; 95% CI, 1.15-2.47; number-needed-to-harm, 29 patients [95% CI, 19–59]).

Up to 5 years, the all-cause death of 3 trials and 863 cases continued to be higher in the paclitaxel-coated arm (14.7%) versus the control arm (8.1%; risk ratio, 1.93; 95% CI, 1.27-2.93—number-needed-to-harm, 14 patients [95% CI, 9–32]).